Integration of singlet oxygen (1O2) detection that provides necessary therapeutic feedback into nanotheranostics for hypoxic tumor photodynamic therapy (PDT) is desirable but still challenging. Herein, we report a nanosensor (denominated PAPD) by combining dual-channel ratiometric sensing and oxygen-augmenting strategies, which synergistically realizes real-time 1O2 self-detection, O2 self-supply and enhanced phototherapy. PAPD nanosensor is constructed by encapsulating anthracene-based 1O2 sensitive fluorophore (DPA) into porphyrin metal-organic frameworks (PCN-224), decorating gold nanoparticles (AuNPs) as nanoenzymes, and coating polyethylene glycol thiol (PEG-SH) by the Au-S bond. PCN-224 serves as 1O2 reference fluorescence (FL) agent and photosensitizer. Once PCN-224-induced 1O2 is synthesized, the dual-channel ratiometric FL signal of PAPD actualizes sensitive, accurate and dynamic 1O2 visualization and gives real-time therapeutic information correlated with the therapeutic progression. Additionally, the catalase-like activity of PAPD possesses in situ O2 production via intracellular H2O2 decomposition and accelerates 1O2 yields for amplifying the tumor cell killing efficiency. Moreover, the ratiometric 1O2 self-detection affords the capacity to evaluate the O2 self-supplying effect in tumor 4T1 cells. Consequently, the rational-designed nanosensor PAPD provides a paradigm for real-time therapeutic evaluation and precise hypoxic tumor treatment clinically.
Keywords: Metal-organic framework; Nanosensor; Oxygen self-supply; Photodynamic therapy; Ratiometric singlet oxygen self-detection.
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